Cell Carcinoma Of Uterine Cervix Research Articles

Dosimetric Comparison of Isodose Surface Volume and Total Reference Air Kerma (TRAK) based Volume in Cervical Cancer Brachytherapy.

We aim to compare TRAK & TPS based isodose volumes in cervical cancer brachytherapy and assess the feasibility, accuracy and potential future implications of TRAK in this regard and as a newer emerging tool to assess treatment intensity in cervical cancer brachytherapy. one hundred patients with histologically proven squamous cell carcinoma of cervix uteri were assessed for brachytherapy (after completion of external radiation) and prospectively enrolled for the study. 60 Gy, 75 Gy, and 85 Gy isodose volumes were obtained from the TPS (VTPS) for 50, 25 & 25 patients with Manchester, Fletcher & interstitial implant respectively, receiving various fractionation schedules by Ir192 HDR remote after-loading system. Using the formula Vpred=4965(TRAK/dref)3/2+170(TRAK/dref)-1.5 the TRAK based isodose surface volumes (Vpred) were derived. Reference doses (dref) were calculated based on accumulated EBRT and brachytherapy doses. The two sets of volume were compared with respect to applicator type, standard, and optimised plan. Surrogate point A dose was also correlated. VTPS - Vpred were 5.24 ± 2.7%, all volumes being predicted within 10%. Correlation of TRAK vs VTPS60/ VTPS75/ VTPS85 showed R2 of 0.994, 0.987 and 0.971 respectively. There was no significant difference in predicted volumes with respect to applicator type. The surrogate point A showed mean volume and standard deviation of 7.44 ± 13.4%, 17.63 ± 16.38 and 3.5 ± 0.95 for Manchester optimised, Fletcher optimised and standard plans respectively. TRAK with point A (R2=0.5632), bladder (R2=0.2015) and rectal doses (R2=0.121) yielded no correlation. Volumes calculated by TRAK correlate with TPS obtained volumes significantly and the formula predicting isodose surface volumes within 10% accuracy for ICBT applications and not for pure interstitial implants. However, TRAK fails to correlate with surrogate point A, bladder and rectal doses hence has questionable utility as a marker for biological response & treatment intensity.

Comparative Study between Two Fractions of 9Gy & Three Fractions of 7Gy High Dose Rate Brachytherapy Following Concurrent Chemo Radiotherapy in Patients with Locally Advanced Carcinoma of Uterine Cervix

Introduction: Traditionally, a judicious combination of external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT) is the widely accepted primary modality of treatment for locally advanced carcinoma of the cervix. Although the recommendation ofAmerican Brachytherapy Society is <7.5 Gyfor individual fraction and four to eight should be the range of fractions; however, literature showed high dose rate (HDR) brachytherapy of two fractions of 9Gyresults in acceptable toxicity without compromising the local control. Methods: This was a Prospective Quasi-Experimental study, conducted in Department of Radiation Oncology, National Institute of Cancer Research and Hospital, Mohakhali, Dhaka from July 2018 to June 2019. Patients with Clinically diagnosed and histopathologically proven squamous cell carcinoma of uterine cervix in locally advanced stage (FIGO stage IIB to IVA) were selected. Total 60 patients were enrolled according to selection criteria and allocated in to group. Both arm was received 50Gy EBRT in 25 fractions with concurrent inj.Cisplatin 40 mg/m2 weekly. Then Arm A was given HDR Brachytherapy 9Gy in each fraction for 2 fractions and Arm B was given HDR Brachytherapy 7Gy in each fraction for 3 fractions. Then treatment responses, locoregional control of disease and acute toxicities were compared between groups. Result:Follow up at 6 months after completion of treatment, complete remission was 90% and 86% respectively for arm A and arm B. The overall complete response was 88%. The common toxicities associated with treatment were bladder and rectal toxicities, skin reaction, small bowel toxicity and haematologic complications which were managed well. During follow up after 6 months, 3 patients in arm A and 2 patients in arm B developed grade II bladder toxicities and only 2 patients in arm A developed rectal grade II toxicities, but there was no rectal toxicity in arm B. Conclusions: Present study showed that a total dose of 18 Gy ICRT in two fractions of 9 Gy over 2 weeks is equally effective in short term local control with acceptable toxicities in comparison with a total dose of 21 Gy in three fractions of 7 Gy ICRT. J Bangladesh Coll Phys Surg 2024; 42: 49-56

Expression of P16ink4a In Cervical Intraepithelial Neoplasia And Invasive Squamous Cell Carcinoma Of Uterine Cervix

Expression of P16ink4a In Cervical Intraepithelial Neoplasia And Invasive Squamous Cell Carcinoma Of Uterine Cervix

Solid Variant of Adenoid Cystic Carcinoma Coexisting with Invasive Squamous Cell Carcinoma in Uterine Cervix – A Case Report with Immunoprofile

Primary adenoid cystic carcinoma of cervix is a rare entity. Co-existence of adenoid cystic carcinoma with squamous cell carcinoma is even more rare. Here we present the case of an 85 year old postmenopausal lady who presented with on and off vaginal bleeding and was found to have a hard cervical mass. Hysterectomy with bilateral salpingo-oophorectomy was done and histopathological evaluation revealed coexisting solid variant of adenoid cystic carcinoma and squamous cell carcinoma. High grade squamous intraepithelial lesion was seen adjacent to invasive squamous cell carcinoma. Adenoid cystic carcinoma was positive for CD117 and squamous cell carcinoma was positive for p63. Both the components were also immunoreactive for p16.

Association of clinico-epidemiological features with locally advanced stage of cervical cancer patients presenting at Bangabandhu Sheikh Mujib Medical University, Bangladesh

Cervical cancer is one of the most prevalent gynecological cancers in women in Bangladesh. The objective of this study was to assess the clincoepidemiological association with the histology of locally advanced cervical cancer. We have done this observational study in the department of Clinical Oncology at Bangabandhu Sheikh Mujib Medical University from July to December 2019. Sixty-six biopsy-proven locally advanced (stage IIB to IVA) squamous cell carcinoma of uterine cervix were included in this study. The mean age of patients at diagnosis was 48.5 (±8.6) years. Commonly observed epidemiological characteristics of locally advanced carcinoma cervix were illiteracy (46.9%), oral contraceptive use (62.1%), multi para (78.7%) and early marriage (74.2%). Most frequent clinical presentation was post-coital bleeding (37.87%). Most patients presented in stage IIB (65.1%). The association of the stages of the disease with age, parity, oral contraceptive use, age at marriage and clinical presentation were statistically nonsignificant, whereas illiteracy was statistically significant. Most women had poor awareness regarding their need for routine check-up and screening as indicated by the late medical care seeking. Social stigma might have played some role. Relevant programmes should create awareness among women, especially those with socioeconomic deprivation. BSMMU J 2022; 15(3): 175-179

Association of IHC p16INK4a expression and ELISA Plasma p16INK4a Protein in Squamous Cell Carcinoma of Uterine Cervix: A Concept of Liquid Biopsy

Introduction: Cervical cancer is the 3rd most common cancer among women worldwide. p16 biomarker is the surrogate marker in cervical cancer and can be detected by Immunohistochemistry (IHC). Aim: To evaluate the association of IHC p16INK4a expression in tissue sections and Enzyme-linked Immunosorbent Assay (ELISA) p16INK4a protein in plasma of paired samples in Squamous Cell Carcinoma (SCC) of uterine cervix. Materials and Methods: This laboratory-based observational, pilot study was conducted at Sri Devaraj Urs Medical College (tertiary health care centre) in South India from June 2020 to May 2021. Total 17 new cases of SCC of cervix diagnosed by histopathology were considered for the study. The cases were staged as per International Federation of Gynecology and Obstetrics (FIGO) staging system and classified by histopathology as keratinising and non keratinising types. IHC p16INK4a evaluation was done on tissue sections and classified as block positivity, ambiguity and negative. ELISA p16INK4a estimation was done using plasma from Dipotassium Ethylenediaminetetraacetic Acid (K2-EDTA) blood sample of same cases. Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 22.0 software. Results: The age ranged from 30-80 years with mean of 54.3±12.0 years. Plasma ELISA p16INK4a level ranged from 3.4-19.6 ng/ mL with a mean of 7.2±2.35 ng/mL in SCC of cervix. The plasma p16INK4a ELISA levels of 5.1 to 6.2 ng/mL, 6.0 to 6.6 ng/mL and 5.5 to 9.7 ng/mL predicts negative, ambiguity and block positivity of IHC p16INK4a expression respectively in corresponding tissue biopsy. Plasma ELISA p16INK4a levels were maximum in Non Keratinising Squamous Cell Carcinoma (NKSCC) followed by Well Differentiated Squamous Cell Carcinoma (WDSCC), Moderately Differentiated Squamous Cell Carcinoma (MDSCC) and Poorly Differentiated Squamous Cell Carcinoma (PDSCC). Conclusion: The plasma ELISA p16INK4a levels and IHC p16INK4a expression were maximum in higher disease stage compared to lower stage. This was a pilot study to evaluate the association between tissue IHC p16 expression and plasma ELISA p16 levels. Further study has to be done on larger study population with standardised procedure to prove the hypothesis.

Evaluation of enzyme-linked immunosorbent assay plasma p16INK4a protein in squamous cell carcinoma in uterine cervix

Cervical cancer is one of the common cancers in females. The common method of screening is Pap test which has low sensitivity. Hence, better methods are explored with different biomarkers, of which estimation of P16 protein can be opted in early detection of cervical cancer. Seventy cases and seventy controls were considered for the study. Cases were invasive squamous cell carcinoma (SCC) of cervix confirmed by histopathology. Controls were healthy age-matched females. The blood sample of cases and controls was collected in K2 Ethylenediaminetetraacetic acid vacutainer, and the separated plasma was subjected to estimation of P16 protein by quantitative sandwich Enzyme-Linked ImmunoSorbent Assay method. The data were analyzed for the association between p16 protein in plasma in cases and controls. The age among cases and controls ranged from 30 to 80 years. The P16 levels among cases ranged from 3.4 to 19.6 ng/ml with a mean of 7.24 ± 2.35 ng/ml. The plasma P16 level in controls ranged between 0.9 and 9.7 ng/ml with mean of 4.1 ± 2.22 ng/ml. At cutoff more than 4.8 ng/ml in cases, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 92.86%, 72.86%, 77.4%, 91.1%, and 82.86%, respectively. The specificity increased with increase in plasma p16 levels. The P16 levels were maximum in stage IV disease. This was a pilot study to detect the plasma p16INK4a levels in SCC of cervix. The levels of plasma p16 protein between 3.9 and 5 ng/ml can be considered as the range for the test to be positive. In clinically suspected cases of cervical cancer, levels more than 4.8 ng/ml can be considered for the diagnosis as point of care test.

The Association between Vascular Endothelial Growth Factor (VEGF) Expression and Various Pathological Parameters of Squamous Cell Carcinoma of Uterine Cervix in Sanglah General Hospital

Cervical cancer is the second most common malignancy in women with increasing morbidity and mortality rate. VEGF is known as one of pro-angiogenic factors that induce angiogenesis in various malignancy. VEGF overexpression is associated with poor prognosis and plays an important role in cervical cancer progression. This study aimed to investigate the association between VEGF expression and pathological parameters of squamous cell carcinoma of uterine cervix in Sanglah General Hospital Denpasar. This is a cross-sectional study design. The sampel size was 36 paraffin blocks which were selected by consecutive sampling. Pathological parameter data were divided into 2 categories; tumor size (£4 cm, >4 cm), tumor extension (intra and extra-uterine), lymphatic vascular invasion (positive, negative), vascular density (low, high) and lymph node metastasis (positive, negative). VEGF expressions were examined by imunohistochemical technique and evaluated by Histo-Score method. All variables were analyzed by Chi-square analysis with significance value p <0.05. Chi-square analysis revealed an association between tumor size and VEGF expression (p=0.035). In addition, large tumor size (>4 cm) has 2.17 times probability of causing high VEGF expression. VEGF expression were not associated with tumor extension (p=0.502), lymphatic vascular invasion (p=0.346), vascular density (p=0.364) and lymph node metastasis (p=0.209). This study has proved that tumor size is associated with VEGF expression. Large tumor size has greater risk of causing high VEGF expression therefore anti-VEGF targeted therapy could be proposed in large tumor size. There were no association between VEGF expression and tumor extension, lymphatic vascular invasion, vascular density and lymph node metastasis.
 
 Keywords: VEGF expression, squamous cell carcinoma, uterine cervix.

Identification of calmodulin-like protein 5 as tumor-suppressor gene silenced during early stage of carcinogenesis in squamous cell carcinoma of uterine cervix.

In the course of identifying the molecular mechanism that is related to strong cell-cell adhesion in stratified structures of the squamous epithelium, calmodulin-like protein 5 (CALML5) was identified as a spinous structure-associated protein by producing monoclonal antibodies with the use of the crude intercellular portion of squamous tissue as an immunogen and by subsequent morphologic screening. By electrophoretic mobility shift assay (EMSA) and a series of mutagenesis studies, two transcription factors, ZNF750 and KLF4, by binding in line to the CALML5 gene promoter, were found to play a central role in CALML5 transcription. Knockdown of CALML5 by siRNA in the A431 cell line that expresses high levels of CALML5 resulted in the acceleration of wound confluence in a scratch assay, indicating that CALML5 functions as a tumor-suppressor in uterine cervical cancer. Immunohistochemical evaluation of squamous intraepithelial lesions, carcinoma in situ (CIS) and invasive uterine cancer, revealed a reduction in CALML5 expression during the stages of CIS through various molecular pathways including the blockage of the nuclear translocation of KLF4. Conversely, restoration of the nuclear translocation of KLF4 by inhibiting ERK-signaling reactivated CALML5 expression in ME180 cells expressing low levels of CALML5. Thus, alteration of the p63-ZNF750-KLF4 axis may result in critical functional loss of CALM-related genes during cancer progression. Although the morphological association of CALML5 with the spiny-structure in relation to cell motility is not clear, evaluation of CALML5 expression provides a useful diagnostic indicator of differentiating dysplasia, preinvasive and invasive cervical cancers.

Papillary squamotransitional cell carcinoma of uterine cervix: A case report

Papillary squamotransitional cell carcinoma [PSTCC] is a lesser-known histological subtype of the most common type of cervical squamous cell carcinoma. Papillary carcinomas of the uterine cervix with transitional or squamous differentiation often resembles transitional cell carcinomas of uterine tract. In the literature, PSTCC is underdiagnosed, has late presentation, is more common in post-menopausal age group and has late recurrences. Here we present a case of PSTCC in 40 years female due to its rare occurrence.

Prognostic significance of poorly differentiated histology and impact of adjuvant chemotherapy in early squamous cell carcinoma of cervix uteri.

ObjectiveThis study is to determine whether the addition of cisplatin‐based chemotherapy after radical hysterectomy will improve the survival of low‐risk squamous cervical carcinoma with poor differentiation.MethodsPatients with low‐risk squamous cervical cancer (FIGO IA2–IIA, absent high‐ and intermediate‐risk factors after pathological evaluation) were eligible for this study. As first, the prognostic relevance of G3 versus G1/G2 among patients with low‐risk squamous cervical cancer was analyzed, then, the oncological results of postoperative chemotherapy among low‐risk squamous cervical cancer with poor differentiation was explored.ResultsTotally, there were 367 low‐risk squamous cervical cancer patients, of whom 161 were poor‐differentiated (47 in the chemotherapy group and 114 in the nonchemotherapy group), with a median follow‐up time of 56 months. Patients with G3 displayed a significantly worse overall survival (p = 0.035), and a higher recurrence rate (p = 0.014) than patients with G1/G2. Compared with the nonchemotherapy group, the hazard ratios (95%CI) for recurrence‐free survival in the chemotherapy group was 0.24 (0.06–0.93), (p = 0.038). No difference in overall survival was observed between the chemotherapy group and the nonchemotherapy group.ConclusionsThe addition of cisplatin‐based chemotherapy following surgery significantly improved recurrence‐free survival for low‐risk, poor differentiation, and early stage squamous cervical cancer patients.

Radiation Response of Cervical Cancer Stem Cells Is Associated with Pretreatment Proportion of These Cells and Physical Status of HPV DNA.

Radio- and chemoresistance of cancer stem cells (CSCs) is considered as one of the possible causes of adverse results of chemoradiotherapy for various malignancies, including cervical cancer. However, little is known about quantitative changes in the CSC subpopulation in the course of treatment and mechanisms for individual response of CSCs to therapy. The purpose of the study was to evaluate the association of radiation response of cervical CSCs with clinical and morphological parameters of disease and features of human papillomavirus (HPV) infection. The proportion of CD44+CD24low CSCs was determined by flow cytometry in cervical scrapings from 55 patients with squamous cell carcinoma of uterine cervix before treatment and after fractionated irradiation at a total dose of 10 Gy. Real-time PCR assay was used to evaluate molecular parameters of HPV DNA. Post-radiation increase in the CSC proportion was found in 47.3% of patients. Clinical and morphological parameters (stage, status of lymph node involvement, and histological type) were not significantly correlated with radiation changes in the CSC proportion. Single- and multifactor analyses revealed two independent indicators affecting the radiation response of CSCs: initial proportion of CSCs and physical status of HPV DNA (R = 0.86, p = 0.001 for the multiple regression model in the whole).

Expression of p16 and Galectin3 in Squamous Cell Carcinoma of Uterine Cervix, in Relation to the Histomorphological Variants: A Cross-sectional Analysis

Introduction: Cancer of uterine cervix comprises a big chunk of cancer registration worldwide. Now-a-days the immunohistochemical marker p16 has emerged as the surrogate marker of high risk Human Papilloma Virus (HPV) infection in cervical tissue. Galectin3, a ubiquitous agent likely to modulate different pro-survival properties necessary for neoplastic cells, is recently emerging as the guardian of tumour microenvironment. Aim: To study the expression of p16 and galectin3 in different histomorphological variants of cervical Squamous Cell Carcinoma (SCC) and their association with grade and stage. Materials and Methods: An observational cross-sectional study was undertaken in the Department of Pathology in a tertiary care hospital in East India, from January, 2019 to June, 2020. Fifty three samples diagnosed as invasive Squamous Cell Carcinoma (SCC) of uterine cervix were taken by systematic random sampling. Immunohistochemical examination was done using monoclonal antibodies against p16 and galectin3 after obtaining thin sections from formalin fixed paraffin embedded blocks and retrieval of antigen. The data was interpreted by light microscopy using a semiquantitative method with respect to prefixed parameters and statistical analysis was done by chi-square test and Fisher’s exact test using SPSS version 25.0. Results: Fifty two out of fifty three cases (98.1%) of squamous cell carcinoma in this study showed almost 100% block posivity of p16 in the tumour cells -strongly corroborative with high risk HPV infection. The non-keratinizing and the basaloid variant showed the strongest intensity of staining (3+). Only one case showed complete negativity of p16 expression. In galectin3 positive cases, strong expression of this marker is found in the invasive tongues of the tumour cells at the junction of tumour stromal interface, consistent with our knowledge regarding the importance of galectin3 in regulating the tumour microenvironment. The strongest galectin3 positivity(3+) was found in the single case of Lymphoepithelioma like squamous cell carcinoma and showed almost 100% positivity among the neoplastic cell population; whereas the non-keratinizing and Basaloid variant showed almost negative expression. Significant association (p=0.00021) found between tumour grade and p16 intensity. Conclusion: The non-keratinizing and basaloid variants of squamous cell carcinoma have shown statistically significant association with highest intensity of p16 staining along with diminished expression of galectin3. Increased tumour grade is also significantly associated with strong staining intensity of p16 and decreased galectin3 expression. However, no significant association is found between galectin3 expression or intensity of p16 expression and the stage of tumour.

Prospective study of apoptotic index and mitotic index as a predictor of response to radiation in subjects of squamous cell carcinoma of uterine cervix treated by radical radiotherapy

Introduction: There exists a wide variation in the response of tumors to radiotherapy and prognosis from individual to individual after radiotherapy to carcinoma of uterine cervix in all stages. Before embarking on treatment one would like to be forearmed with the knowledge that the treatment outcome would be good. Apoptosis is an important mechanism in predicting response to radiotherapy in squamous cell carcinoma of uterine cervix. Objective: Prospective study to correlate the relation between markers of cell proliferation (MI), cell death (AI), and MI to AI ratio as an independent prognostic factors in patients of carcinoma of uterine cervix treated by radical radiotherapy. Materials and Methods: 56 evaluable subjects of squamous cell carcinoma of uterine cervix during the period from May 1999 to December 1999 were enrolled in the study and patients were followed for 2 years. Measurement of Apoptotic index (AI) and Mitotic Index (MI) was done by microscopic method only. All subjects received radiation to a dose of 70 Gy using standard technique. Results: Patients with Apoptotic Index (AI) less than median value of 0.75% and Mitotic Index (MI) greater than median value of 0.2% showed better response to radical radiation therapy at 2 years. However the difference is not statistically significant (p = 0.20 and 0.25 respectively). Patients with AI/MI less than median value of 0.3 showed better local as well as overall control of disease when compared to patients with AI/MI ratio greater than median value of 0.3. The difference is statistically significant (p = 0.03). Conclusions: Besides traditional prognostic factors like stage, lympho-vasular invasion, AI/MI ratio will provide a guide for response to radiotherapy and prognosis. Keywords: Apoptosis index, Mitotic index, Apoptosis index to mitotic index ratio, Squamous cell carcinoma of uterine cervix, Response to radiation therapy and prognosis.

PET Radiomics Analysis for Prediction of Metabolic Complete Response of Primary Tumor After Chemo-Radiotherapy for Squamous Cell Carcinoma of Cervix Uteri

PET Radiomics Analysis for Prediction of Metabolic Complete Response of Primary Tumor After Chemo-Radiotherapy for Squamous Cell Carcinoma of Cervix Uteri

Role of Radiomics and Advanced MR Imaging (Diffusion MRI) in Predicting Clinical Prognostication of Uterine Cervix Carcinoma

Radiation with concurrent chemotherapy forms the cornerstone of management for International Federation of Gynecology and Obstetrics (FIGO) stage IB2 to IVA uterine cervix carcinoma disease. Radiomics has emerged as a promising tool for imaging biomarker discovery in era of precision medicine. We explored potential of Radiomics alone and in combination with diffusion imaging derived quantitative parameter namely apparent diffusion co-efficient (ADC) using supervised classification algorithms in predicting outcomes and prognosis. Retrospective evaluation of the imaging was done for a study cohort of 52 patients of squamous cell carcinoma of uterine cervix who were candidates for radical treatment with chemo radiation. One radiologist having 6 years of experience manually drew the region of interest on the tumor for purposes of segmentation and textural analysis. ADC values were calculated from conventional from the darkest part of the tumor, both before (labelled ADC1) and post treatment (labelled ADC2) with chemo radiation. The segmented tumor was validated independently by two radiologists having 30 years of experience each. A total of 851 Radiomics features were extracted from the available imaging using slicer 3D software and open source software. Feature selection was done by taking the union of the features which had Pearson correlation > 0.35 for recurrence > 0.35 for lymph node and > 0.49 for Stage. Models were trained to predict the clinical outcomes using leave one out cross-validation and different algorithms. Using Radiomics features alone building a monotype multilayer perceptron neural network models for predicting recurrence we were able to achieve an accuracy of 85%. The Kappa score (0.55) and the area under the curve (AUC) was 0.80. Using baseline ADC values and change in ADC during treatment in combination with Radiomics features yielded better AUC of 0.82. Using Monotype multilayer perceptron neural network to determine stage (accuracy 60%, kappa 0.38 and AUC 0.75) were achieved when Radiomics was used alone. For predicting lymph node status, we used Nearest Shrunken Centroids model to achieve an accuracy of 81 % and AUC of 0.76 combining Radiomics, change of ADC and baseline ADC. Further on dividing the patients into 2 groups (based on extensive loco-regional disease with distant metastasis (18) vs good response (34) we found that 3 Radiomics wavelet features showed significant statistical difference. The study is an effort to bridge the unmet need of translational predictive biomarkers in stratification of uterine cervix cancer patients based on prognosis. Radiomics features on imaging could be vital in prognostication and prediction of recurrence.

Expression of P16 biomarker in squamous cell carcinoma of uterine cervix and its association with clinico-pathological parameters: A cross-sectional study

Introduction: Cervical cancer is the most common cancer among females. P16 is the surrogate marker for cervical carcinoma. This study aimed to evaluate the association of P16 marker with clinic-pathological parameters in squamous cell carcinoma of uterine cervix.
 Methods: This was a cross-sectional study. Histological confirmed cases of squamous cell carcinoma (SCC) of cervix were considered. All cases were evaluated for IHC P16 expression as per lower anogenital squamous terminology (LAST) criteria and correlated with clinico-pathological parameters. The data was analyzed by SPSS software version 22.
 Results: Out of 75 cases, P16 biomarker expression was block positive, ambiguous and negative in 67 (89.3%), 5 (6.6%), and 3 (4%) cases, respectively. There was a significant association between P16 expression and age (p = 0.005). All cases between 30-59 years of age showed block positivity. There was no significant association between P16 expression and age at marriage (p = 0.951), age at menopause (p = 0.311), parity (p = 0.554), clinical symptoms/signs, stage of disease (p = 0.28), or histopathological grade (p = 0.877). Maximum expression was seen between 40-44 years. Moreover, all cases having 1 & 2 parity showed block positivity and all stage I cases showed block positivity.
 Conclusion: P16 biomarker was significantly expressed in cervical cancers of the relatively younger age group and those with early stage of disease.

To analyse target volume variations during SIB-IMRT of squamous cell carcinoma of uterine cervix

AbstractPurpose:To assess volume variations in target site due to changes in bladder filling and rectal content including air bubbles during simultaneous-integrated boost intensity-modulated radiotherapy (SIB-IMRT) of patients suffering from squamous cell carcinoma of uterine cervix.Materials and methods:A total of ten patients of squamous cell carcinoma of uterine cervix were enrolled in this analysis. All patients were planned to undergo SIB-IMRT using 10 MV beam. Planning target volume of the tumour (PTVtumour) and PTVnodal were prescribed with 5,040 and 4,500 cGy doses, respectively. During planning, PTVtumour V95%, PTVnodal V95% and organs at risk (OARs) (bladder, rectum, femoral heads and small bowel) volumes were measured from initial CT planning scans taken with full bladder. CT scans were acquired once in a week over a treatment period of 5·5 weeks. Intra-treatment scans with full bladder were then fused with the planning scans to determine variations in the target volume and the OAR volume. Changes in radiation dose to the PTVtumour and the PTVnodal were also assessed by comparing intra-treatment scans with the planning (first) scans.Results:All patients showed intra-treatment bladder volume larger than the planning bladder volume. Difference between planning bladder and intra-treatment bladder volumes ranged from 4·5 to 49%. Rectal volume varied from 17 to 60 cc. A wide variation between planning and intra-treatment air volumes was found in most of the patients. When comparing initial and inter-fraction air volumes, the maximum difference was 366·67%. Due to bladder and rectal volume variations, PTVtumour V95% and PTVnodal V95% doses did not remain constant throughout the treatment. The maximum discrepancy between intra-treatment PTVtumour dose and planning PTVtumour dose was 12·15%. The maximum difference between planning and inter-fraction PTV V95% was 48·28%. PTVnodal dose observed from scan taken in last week of treatment was 12·87% less than planning PTVnodal dose analysed from planning CT scan. Maximum difference in planning and inter-fraction PTVnodal V95% was 57·78%.Conclusion:Inconsistent bladder and rectal volumes had a significant impact on target volume and dosage during an entire course of SIB-IMRT. For radiotherapy of gynaecological malignancies, data on variations in PTV should be acquired on daily basis to target radiation dose to the tumour site with accuracy.

Clinicopathological correlation of invasive squamous cell carcinoma of uterine cervix: A cross-sectional study

Objective: Cervical cancer is a common cancer in females. Clinicopathological features vary and are heterogeneous in different studies. This study was taken up to know the clinicopathological correlation in squamous cell carcinoma (SCC) of the cervix in our population. Methods: This is a cross-section study. Histologically confirmed cases of squamous cell carcinoma of the cervix are considered. Clinical history, socio-demographic details, clinical findings including stage and histological grade of the disease are noted and statistically analyzed. Result: The age range of cases was 30-80 years, with a mean of 54.2+/-12.0. The age range at marriage was 12-23 years, with a mean of 15.7+/-2.1. Parity ranged from 1 to 11, with a mean of 3.6+/-1.6. The p-value between bleeding pervagina and other symptoms versus no bleeding per-vagina and other symptoms, stage of disease between pre & peri-menopausal, and post-menopausal cases were 0.011 and 0.020, respectively. Growth followed by bleeding was common clinical findings. The p-value between the stage of the disease and age, histological grade and parity, histological grade and clinical features was 0.032, 0.001, and 0.031 respectively. Conclusion: Younger age group cases and pre & peri-menopausal women present the disease at an early stage. Older age women present at an advanced stage. Higher parity had a higher risk of cervical cancer of well differentiated SCC. Bleeding per-vagina was a more common clinical presentation in post-menopausal women. Clinical features of bleeding per vagina with other symptoms were more common in well differentiated SCC.

Molecular Analysis as a Guide to Determining the Extent and Pathophysiology of Perilesional Tissues in Oral Epithelial Dysplasias

Clinically and histologically normal appearing perilesional mucosa of epithelial dysplasia may harbor early genetic changes. Hence, the present study is designed to determine the early molecular changes in the form of p16 and EGFR immunoexpressions in perilesional tissues. To analyze immunohistochemical expressions of p16 and EGFR individually and percentage change of immunoexpressions in oral dysplastic lesions and their perilesional tissues. Forty formalin-fixed paraffin-embedded tissues of oral epithelial dysplasia with perilesional tissue marked by India ink were included in this study. Immunohistochemical staining was performed using anti-p16 and anti-EGFR monoclonal antibodies (BioGenex) using squamous cell carcinoma of uterine cervix and breast carcinoma as the positive controls, respectively. p16 and EGFR expressions were assessed based on the presence, intensity, extent and immunolocalization of positive cells. Out of 40 cases, p16 immunoexpression was positive in 82.5% cases of lesional tissues and in 62.5% cases of perilesional tissues (p ≤ 0.05); however, EGFR immunoexpression was positive in 90% cases of both lesional and perilesional tissues (p > 0.05). The disease status and progression based on p16 and EGFR expressions and co-expressions can be used as an effective guide to evaluating the progression of normal epithelium to dysplastic epithelium in otherwise clinically normal mucosa.